Cv- Lipid Lowering Agents

Front 1

What are the steps of lipoprotein production?

Back 1

1. liver generates triglycerides and cholesterol, which form VLDL's
2. VLDL's move from the liver to the endothelial cells of skeletal muscle and fat
3. lipoprotein lipase breaks down the VLDL's to form IDL's
4. IDL's can either be taken up into the liver or converted to LDL's
5. LDL's can either be taken up into the liver or transported to extrahepatic tissue, where it is delivered as cholestrol

Front 2

What are the 3 sources of cholesterol in the liver?

Back 2

1. food
2. LDL’s from the blood
3. de novo synthesis

Front 3

How is dietary fat taken up into the liver?

Back 3

dietary fat->broken into fats and triglycerides by lipoprotein lipase->chylomicron remnant is taken up at liver's remnant receptor->cholesterol is delivered to the liver

Front 4

What are 2 things that cholesterol can be used to make?

Back 4

1. VLDL's
2. bile acids

Front 5

What is the process of de novo synthesis?

Back 5

HMGCoA->HMGCoA reductase->mevalonate->->cholesterol

Front 6

How are LDL's uptaken into the liver?

Back 6

LDL's in blood->bind to liver's LDL receptor->cholesterol into the liver

Front 7

What is the MOA for statins?

Back 7

HMGCoA reductase blocks HMGCoA->inhibits de novo synthesis->LDL receptors are upregulated->more LDL is taken up by the liver

Front 8

What effect do HMGCoA reductase inhibitors have on LDL's? Triglycerides? HDL's?

Back 8

1. large effect
2. modest effect
3. modest effect

Front 9

When does the greatest LDL-lowering effect occur with the use of HMGCoA reductase inhibitors? How much does this increase by doubling?

Back 9

1. normal starting dose
2. 6% at each doubling

Front 10

How are statins metabolized?

Back 10

cytochrome P450 enzymes (grapefruit inhibits these)

Front 11

Which 2 statins have the longest 1/2 life? What about the rest?

Back 11

1. atorvastatin
2. rosuvastatin
3. ~4 hours

Front 12

What is the major cardioprotective effect of statins?

Back 12

lowers LDL and VLDL

Front 13

What are 5 non-lipid cardioprotective effects of statins?

Back 13

1. decrease inflammation (CRP)
2. increase endothelial function
3. increase plaque stability
4. decrease lipoprotein oxidation
5. decrease platelet aggregation

Front 14

Which 4 statins are taken at night? Why?

Back 14

1. all except atorvastatin and rosuvastatin
2. taken at night because no dietary fats are ingested->increases de novo synthesis->increased blocking of HMGCoA reductase->max effect

Front 15

What are some adverse effects of statins?

Back 15

1. GI problems
2. elevated transaminases
3. myalgia
4. myopathy
5. rhabdomyolysis

Front 16

T or F: progression of elevated transaminases to hepatotoxicity occurs frequently with statin use

Back 16

false, this is rare

Front 17

What is myopathy?

Back 17

myalgia with CK 10x high normal level

Front 18

What is rhabdomyolysis?

Back 18

extensive skeletal muscle damage with myoglobinuria (brown urine)

Front 19

When taking statins, what drugs can cause increased incidence of myopathy?

Back 19

1. fibrates (gemfibrozil)
2. niacin (rarely)
3. CYP3A4 inhibitors (cyclosporine, azoles, and erythromycin)

Front 20

Which statin was taken off the market?

Back 20

cerivastatin-increased myopathy and rhabdomyolysis

Front 21

What are 2 contraindications for giving statins?

Back 21

1. hepatic disease (due to increased risk of hepatotoxicity)
2. pregnancy (due to need for lipid membrane formation)

Front 22

What grocery store item used to have lovastatin or similar compounds in it?

Back 22

red yeast rice

Front 23

What are the 3 bile acid binding resins?

Back 23

1. cholestyramine
2. colestipol
3. colesevelam

Front 24

Where do bile acids go?

Back 24

liver->intestines->liver

Front 25

What is the MOA of bile acid binding resins?

Back 25

bile acids go to intestine->resin contains Cl->bile acid exchanges with Cl->bile acid is excreted->more cholesterol must be used to make bile acids

Front 26

How does the liver meet the increased cholesterol demand in the case of BABR's?

Back 26

1. increased de novo synthesis
2. increased LDL receptors

Front 27

Would you combine a bile acid binding resin with a statin?

Back 27

yes

Front 28

What is the overall effect of bile acid binding resins on LDL's? Triglycerides? HDL's?

Back 28

1. moderate decrease
2. transient increase (unless hypertriglyceridemia hx)
3. small increase

Front 29

What is a major problem with BABR's?

Back 29

poor compliance due to dose frequency and powder form

Front 30

What 2 things are BABR's taken for?

Back 30

1. hypercholesterolemia
2. improvement of glycemic control in DM

Front 31

During what timeframe should you take BABR's?

Back 31

before eating (this drug only works when bile is present during eating)

Front 32

What are 3 adverse effects of taking BABR's?

Back 32

1. GI problems
2. impaired absorption of anionic drugs
3. impaired absorption of vitamins A, D, and K

Front 33

When should you take other drugs in relation to BABR's?

Back 33

1 hour before or 4 hours after taking the BABR

Front 34

What is the name of the cholesterol absorption inhibitor?

Back 34

ezetimibe

Front 35

What is the MOA of ezetimibe?

Back 35

prevents absorption of cholesterol in the intestinal villi->decreased delivery of cholesterol to liver

Front 36

T or F: ezetimibe does not alter intestinal TG or fat-soluble vitamin absorption

Back 36

true

Front 37

What is the overall effect of ezetimibe on LDL's? Triglycerides? HDL's?

Back 37

1. modest decrease of LDL's
2. small effect on triglycerides or HDL's

Front 38

What are cholesterol absorption inhibitors used for?

Back 38

1. hypercholesterolemia
2. monotherapy if indicated
3. in combo with a statin to either lower the statin dose or add on to the max dose of statin
4. in combo with fibric acid

Front 39

What is the effect of using a cholesterol absorption inhibitor in conjunction with a statin?

Back 39

better lowering of LDL

Front 40

What is the adverse effect of ezetimibe?

Back 40

GI problems

Front 41

What was the MOA of niacin once thought to be?

Back 41

1. in adipocytes, hormone sensitive lipase breaks triglycerides into free fatty acids for uptake into the liver
2. niacin binds to GPR109A receptor, which causes inhibition of HSL
3. this results in less free fatty acids for liver uptake->less triglyceride synthesis

Front 42

What is the current thinking on the MOA of niacin?

Back 42

1. in hepatocytes, DGAT2 is needed to create triglycerides, which are needed to make VLDL's
2. also in hepatocytes, ApoB is needed to make VLDL's
3. niacin blocks DGAT2
4. end result is less ApoB lipids (VLDL and LDL) and production of larger LDL's

Front 43

Why is it important to shift from small, dense LDL's to large, buoyant LDL's?

Back 43

small, dense LDL's are more atherogenic

Front 44

What are the overall effects of niacin on LDL's? Triglycerides? HDL's? Lp(a)?

Back 44

1. moderate decrease
2. large decrease
3. large increase
4. decrease (may be atherogenic lipoprotein)

Front 45

What is niacin used for?

Back 45

1. hypertriglyceridemia
2. mixed hyperlipidemia
3. hypercholesterolemia

Front 46

What triglyceride level would prompt prescribing niacin? What drug can be used to enhance effectiveness? What is the overall effect of this adjunct?

Back 46

1. >500
2. statin
3. works better to lower LDL, triglycerides, and raise HDL

Front 47

Why would you titrate niacin?

Back 47

reduce niacin flush occurrence

Front 48

What would happen if you combined cholestyramine with niacin?

Back 48

niacin helps to lower triglycerides and raise HDL's; cholestyramine would help to lower LDL's

Front 49

What drug will work to decrease PG-mediated vasodilation that occurs with niacin?

Back 49

ASA

Front 50

Do flush-free niacin meds work?

Back 50

no-they lack free nicotinic acid

Front 51

In what ways do the the different niacin preps affect niacin flush?

Back 51

1. immediate release-more flushing, less hepatotoxic
2. sustained release-less flushing, more hepatotoxic
3. extended release-less flushing, less hepatotoxic, more costly

Front 52

What are some adverse effects of niacin?

Back 52

1. niacin flush
2. GI problems
3. hepatotoxicity
4. abnormal liver function tests
5. hyperglycemia (in high doses)
6. hyperuricemia

Front 53

What are the contraindications for niacin?

Back 53

1. chronic liver disease
2. active peptic ulcer
3. gout
4. high doses in DM

Front 54

What are the 3 fibric acid derivatives?

Back 54

1. gemfibrozil
2. fenofibrate
3. fenofibric acid

Front 55

What is the MOA of fenofibrate?

Back 55

increases activity of PPAR-alpha->increased lipoprotein lipase->decreases triglycerides, VLDL's, and small, dense LDL's

Front 56

What is the overall effect of fenofibrate on LDL's? Triglycerides? HDL's?

Back 56

1. modest increase/decrease
2. large decrease
3. moderate to large increase

Front 57

What are fibric acid derivatives used for?

Back 57

hypertriglyceridemia

Front 58

What are the adverse effects of fibric acid derivatives?

Back 58

1. GI problems
2. gall stones (clofibrate)
3. myopathy and rhabdomyolysis (w/statins)

Front 59

What affect do omega-3-fatty acids have on triglycerides? LDL's?

Back 59

lowers triglycerides but raises LDL's

Front 60

What is an adverse effect of omega-3-fatty acids?

Back 60

malodorous eructation (bad-smelling belches)